Safety and Immunogenicity Study of Recombinant Thrombin (rThrombin) in Pediatric Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ZymoGenetics
ClinicalTrials.gov Identifier:
NCT00859547
First received: March 9, 2009
Last updated: January 25, 2012
Last verified: January 2012

March 9, 2009
January 25, 2012
March 2009
January 2010   (final data collection date for primary outcome measure)
  • Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity [ Time Frame: Days 1 through 29, continuously ] [ Designated as safety issue: Yes ]
    An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment
  • Number of Participants With AEs by Maximum Severity [ Time Frame: Days 1 through 29, continuously ] [ Designated as safety issue: Yes ]
    An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. Mild=asymptomatic or minor symptoms; intervention not indicated. Moderate=requiring only minimal, local, or noninvasive intervention. Severe=significant symptoms but not life-threatening; hospitalization or invasive intervention indicated. Life-threatening=indicating intensive care or urgent invasive intervention.
  • Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts [ Time Frame: Baseline and Day 29 from Baseline ] [ Designated as safety issue: Yes ]
    Abnormal laboratory findings were recorded as AEs when considered clinically significant (unusual for the surgical population or individual participant) by the investigator, when associated with symptoms, when requiring specific treatment, or when requiring a change in participant management.LLN=lower level of normal. Platelets: Grade 0=normal. WBC: Grade 0=normal. Lymphocytes: Grade 0=normal; Grade 1=<LLN x 0.8-10^9/L. Neutrophils: Grade 0=normal; Grade 1=<LLN-1.5x10^9/L; Grade 2=<1.5-1.0x10^9/L
  • Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels [ Time Frame: Baseline and Day 29 from Baseline ] [ Designated as safety issue: Yes ]
    LLN=lower level of normal. Grade 1=100 g/L to <LLN; Grade 2=80 to <100 g/L; Grade 3=65 to <80 g/L; Grade 4=<65 g/L.
  • Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Creatinine Levels [ Time Frame: Baseline and Day 29 from Baseline ] [ Designated as safety issue: Yes ]
    ULN=upper level of normal. Grade 0=normal; Grade 1=>ULN to 1.5 x ULN.
  • Number of Participants With Elevations in the Coagulation Parameter of Activated Partial Thromboplastin Time (aPPT)of Grade 0 or Higher [ Time Frame: Baseline and Day 29 from Baseline ] [ Designated as safety issue: Yes ]
    ULN=upper limit of normal. Grade 0=normal; Grade 1=ULN to 1.5 x ULN.
  • Number of Participants With a High International Normalized Ratio (INR) of Prothrombin Time of Grade 0 or Higher [ Time Frame: Baseline and Day 29 from Baseline ] [ Designated as safety issue: No ]
    Grade 0=normal.
Adverse events, including standard clinical laboratory abnormalities [ Time Frame: Through Day 29 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00859547 on ClinicalTrials.gov Archive Site
Number of Participants WIth Positive Findings for Anti-rThrombin Product Antibody [ Time Frame: At Day 29 ] [ Designated as safety issue: No ]
Antibody-positive was defined as seroconversion or ≥1.0 unit (≥10-fold) increase in titer compared with antibody titer at baseline.
Incidence of anti-rThrombin product antibody development [ Time Frame: Day 29 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Safety and Immunogenicity Study of Recombinant Thrombin (rThrombin) in Pediatric Participants
A Phase 4, Open-Label, Single-Group Safety and Immunogenicity Study of RECOTHROM® (rThrombin) in Pediatric Subjects Undergoing Synchronous Burn Wound Excision and Skin Grafting

The objective of this study is to assess the safety and immunogenicity of recombinant thrombin (rThrombin) administered as an aid to hemostasis during burn wound excision and skin grafting in pediatric patients, newborn through 17 years of age.

The safety, immunogenicity, and efficacy of rThrombin have been evaluated in 5 Phase 2 studies, 1 pivotal Phase 3 study, and 1 Phase 3b study, in surgical indications such as: spinal surgery, major hepatic resection, peripheral arterial bypass surgery, arteriovenous graft formation for hemodialysis access, and burn wound excision. Limited data currently exist on the effects of rThrombin exposure in pediatric patients. This Phase 4 trial aims to provide additional information on the use of rThrombin in children by evaluating the drug's safety and immunogenicity when administered as an aid to hemostasis during burn wound excision and skin grafting in pediatric burn patients.

Interventional
Phase 4
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Blood Loss, Surgical
Biological: rThrombin, 1000 IU/mL
rThrombin,1000 IU/mL, 1000 IU/mL, applied topically to the bleeding site during a single surgery procedure on Day 1.
Other Name: RECOTHROM
Experimental: Recombinant thrombin (rThrombin), 1000 IU/mL
Intervention: Biological: rThrombin, 1000 IU/mL
Foster KN, Mullins RF, Greenhalgh DG, Gamelli RL, Glat P, Lentz CW, Kahn SA, Brandigi C, Fredlund P, Alexander WA. Recombinant human thrombin: safety and immunogenicity in pediatric burn wound excision. J Pediatr Surg. 2011 Oct;46(10):1992-9. doi: 10.1016/j.jpedsurg.2011.05.022.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
January 2010
January 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age of newborn through 17 years at time of enrollment
  • At least 1 skin graft recipient site measuring at least 1% of total body surface area (TBSA)
  • Total initial burn wounds estimated to measure less than 40% of TBSA
  • Bleeding indicating treatment with rThrombin during the surgical procedure
  • Females of child-bearing potential must have a negative urine or serum pregnancy test within 2 days prior to study-drug treatment
  • informed consent document signed by legal representative (guardian) and approved by an institutional review board/independent ethics committee (IRB/IEC)
  • Participant has signed an IRB/IEC-approved pediatric assent document, if applicable

Exclusion Criteria:

  • Gestational age younger than 36 weeks at birth (for infants younger than 2 years)
  • Documented active infection at the graft recipient site (participants with resolved infections at potential graft recipient sites are not excluded)
  • Acute inhalation injury, as defined by bronchoscopic evidence of lower airway injury
  • Currently undergoing autologous skin grafting for ischemic ulcer disease or cutaneous malignancies
  • Presence of antibodies or hypersensitivity to the study drug or any of its components, other thrombin preparations, or coagulation factors
  • Transfusion of whole blood, fresh frozen plasma, cryoprecipitate, or platelets within 24 hours prior to study-drug treatment (packed red blood cell transfusions are allowed)
  • History of HIV infection or other immunodeficiency syndrome or is taking immunosuppressive or antirejection medications
  • Medical, social, or psychosocial factors that, in the opinion of the investigator, could affect safety or compliance with study procedures
  • Breastfeeding or being breastfed
  • Treatment with any experimental agent within 30 days of study enrollment or treatment
Both
up to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00859547
499H01
Yes
ZymoGenetics
ZymoGenetics
Not Provided
Principal Investigator: Kevin Foster, MD Arizona Burn Center
ZymoGenetics
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP